此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

肝移植后甲苯磺酸索拉非尼治疗肝癌患者

2026年10月9日 更新者：Jonsson Comprehensive Cancer Center

索拉非尼辅助治疗肝细胞癌 (HCC) 高危原位肝移植 (OLT) 受者的 II 期随机多中心安慰剂对照盲法研究

The purpose of this study is to determine if sorafenib (sorafenib tosylate) is a safe and effective treatment option for preventing liver cancer in high risk patients following liver transplantation. Liver transplantation is a treatment option for liver cancer patients, but despite transplantation, the liver cancer can recur in the new, transplanted liver. It is not known whether sorafenib is effective in preventing cancer recurrence in high risk patients following liver transplantation

研究概览

地位

完全的

条件

干预/治疗

详细说明

PRIMARY OBJECTIVES:

I. Two-year recurrence free survival (RFS).

SECONDARY OBJECTIVES:

I. One-year recurrence free survival. II. Overall survival (OS). III. Safety. IV. Impact of drug-drug interactions (i.e. immunosuppression agents). V. Impact of biomarkers (alpha-fetoprotein [AFP], protein-induced by vitamin K absence or antagonist II [PIVKA II]).

VI. Effects of therapy on wound healing. VII. Impact of hepatitis C viral recurrence.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive sorafenib tosylate orally (PO) twice daily (BID).

ARM II: Patients receive placebo PO BID.

In both arms treatment continues for 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years.

研究类型

介入性

注册 (实际的)

73

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • Alabama
      • Birmingham、Alabama、美国、35294-0007
        • University of Alabama
    • California
      • Los Angeles、California、美国、90095
        • Jonsson Comprehensive Cancer Center
    • Colorado
      • Denver、Colorado、美国、80217-3364
        • University of Colorado
    • Connecticut
      • Hartford、Connecticut、美国、06112
        • Mount Sinai Hospital
    • District of Columbia
      • Washington D.C.、District of Columbia、美国、20057
        • Lombardi Comprehensive Cancer Center at Georgetown University
    • Georgia
      • Atlanta、Georgia、美国、30322
        • Emory University
    • Illinois
      • Chicago、Illinois、美国、60611
        • Northwestern University
    • Louisiana
      • New Orleans、Louisiana、美国、70121
        • Ochsner Clinic Foundation
    • Maryland
      • Baltimore、Maryland、美国、21287-8936
        • Johns Hopkins University
    • Massachusetts
      • Burlington、Massachusetts、美国、01805
        • Lahey Clinic Medical Center
    • Michigan
      • Ann Arbor、Michigan、美国、48109
        • University of Michigan University Hospital
    • Nebraska
      • Omaha、Nebraska、美国、68198-7830
        • University of Nebraska Medical Center
    • New Jersey
      • Cherry Hill、New Jersey、美国、08034
        • University of Pennsylvania Health System
    • New York
      • New York、New York、美国、10016
        • New York University Langone Medical Center
      • New York、New York、美国、10065
        • New York Presbyterian-The University Hospital of Columbia and Cornell
    • Ohio
      • Cleveland、Ohio、美国、44195
        • Cleveland Clinic Foundation
    • Oklahoma
      • Oklahoma City、Oklahoma、美国、73112
        • Integris-Baptist Medical
    • Pennsylvania
      • Pittsburgh、Pennsylvania、美国、15213
        • University of Pittsburgh
    • Tennessee
      • Nashville、Tennessee、美国、37232
        • Vanderbilt University
    • Texas
      • Houston、Texas、美国、77030
        • Baylor College of Medicine
      • Houston、Texas、美国、77030
        • The Methodist Hospital Research Institute

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

19年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Patients must have hepatocellular carcinoma (HCC) with one of the following on explant: microvascular/macrovascular invasion, tumor outside of Milan criteria, poor tumor differentiation; patients with macrovascular invasion on explant pathology will be stratified

    * Additionally, the following will be included

    ** Patients with elevated surrogate markers (AFP > 500 or PIVKA > 400) pre transplant and with biopsy proven HCC prior to orthotopic liver transplantation (OLT) or on explant

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2

  • Patients with a life expectancy > 12 weeks

  • Patients must have completed prednisone taper within 6 weeks post OLT

  • Patients must be enrolled between 6 to 12 weeks post OLT

  • Cadaveric donors only (no living donor liver transplantation [LDLT] or donor after cardiac death transplantation [DCDT])

  • No sorafenib prior to inclusion in the study

  • Platelet count > 50 x 10^9/L

  • Hemoglobin >= 8.5 g/dL

  • Total bilirubin =< 5 mg/dL

  • Alanine transaminase (ALT) and aspartate aminotransferase (AST) =< 5 x upper limit of normal

  • Amylase and lipase =< 1.5 x the upper limit of normal

  • Serum creatinine < 2 x the upper limit of normal

  • Prothrombin time (PT) =< 6 seconds or international normalized ratio (INR) =< 2.3

  • AFP > 500 (pre-transplant)

  • PIVKA > 400 (pre-transplant)

  • Patient has not received prior anti-angiogenic therapy, systemic targeted agents or systemic chemotherapy

    * Prior surgical resection, chemoembolization or other local therapy prior to transplant is permitted

  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test

  • Patients (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 30 days after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate

  • Patient must be able to swallow and retain oral medication

  • Patient must exhibit the ability to understand and willingness to sign a written informed consent regarding the study and alternative treatments

Exclusion Criteria:

  • Significant ongoing immunologic rejection based on pathology and clinical diagnosis (from time of transplant until randomization)

  • Use of T cell depleting agents for prevention or treatment of rejection at any point prior to or after enrollment in the study

  • Patient with documented evidence of metastatic disease

  • 100% tumor necrosis on explant pathology

  • Use of mammalian target of rapamycin (mTOR) inhibitors prior to transplant and as post-transplant immunosuppression

  • Use of alemtuzumab

  • Living donor liver transplant (LDLT) or donation after cardiac death transplant (DCDT)

  • Human immunodeficiency virus (HIV) positive patients

  • Hepatitis C virus (HCV) recurrence at the time of randomization

  • Use of direct acting antivirals for HCV recurrence

  • Requirement of re-transplantation for primary non function

  • Uncontrolled hypertension, defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management

  • Active or clinically significant cardiac disease including:

    • Congestive heart failure - New York Heart Association (NYHA) > class II
    • Coronary artery disease
    • Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
    • Unstable angina or new-onset angina within 3 months before randomization, or myocardial infarction (MI) within 6 months before randomization

  • Clinically active serious infection documented by positive cultures or an incomplete course of treatment for bacteremia or fungemia

  • Evidence or history of bleeding diathesis or coagulopathy

  • Patients with any pulmonary hemorrhage/bleeding event grade 2 or higher within 4 weeks before randomization

  • Patients with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks [TIAs]) within 6 months before randomization

  • Prior use of raf-kinase inhibitors (sorafenib), vascular endothelial growth factor (VEGF) inhibitors, mitogen-activated protein kinase (MAPK)/extracellular-signal-related kinase (ERK) kinase (MEK) inhibitors, or farnesyl transferase inhibitors

  • Patients using cytochrome P450 3A4 (CYP3A4) inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John's Wort dexamethasone) at a dose of greater than 16 mg daily, or rifampin and/or rifabutin within 28 days before randomization

  • Patients with non-HCC malignancy except those with DCIS (ductal carcinoma in situ), cervical cancer in-situ, basal cell or superficial bladder tumor; patients surviving a cancer that was curatively treated and without evidence of recurrence for more than 3 years before randomization are allowed

  • Presence of a non-healing wound, non-healing ulcer, or bone fracture

  • Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial

  • Any malabsorption condition

  • Women who are pregnant or breast-feeding

  • Inability to comply with the protocol and/or not willing or not available for follow-up assessments

  • Patients with fibrolamellar HCC, cholangiocarcinoma, and combined HCC-cholangiocarcinoma

  • Any condition which, in the investigator's opinion, makes the patient unsuitable for trial participation

  • Prior use of any systemic chemotherapy for HCC

  • Prior use of systemic investigational agents for HCC

  • Prior use of raf-kinase inhibitors (sorafenib), VEGF inhibitors, MEK inhibitors or farnesyl transferase inhibitors

  • Use of biologic response modifiers, such as granulocyte colony-stimulating factor (G-CSF), will not be permitted within 3 weeks prior to study entry; G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity, such as febrile neutropenia, when clinically indicated or at the discretion of the investigator; however, they may not be administered to prevent a dose reduction; patients taking chronic erythropoietin are permitted, provided no dose adjustment is undertaken within 1 month prior to randomization or during the study

  • Autologous bone marrow transplant or stem cell rescue within four months of start of study drug

  • Concomitant treatment with rifampin and St. John's wort

  • Concomitant oral mTOR inhibitor treatment

  • Use of direct acting antivirals for HCV recurrence

  • Use of T-cell depleting agents

  • Use of alemtuzumab

  • Anticoagulation, as described below, is allowed:

    • Vitamin-K antagonists (e.g., warfarin)

      ** Low dose warfarin (1 mg orally, once daily) with PT-INR =< 1.5 x ULN is permitted; patients taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes

    • Low dose aspirin (=< 100 mg daily).

    • Heparins and heparinoids Use of any other investigational drug

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：单身的

武器和干预

参与者组/臂
干预/治疗
实验性的：Arm I (sorafenib tosylate)

Patients receive sorafenib tosylate PO BID.
其他：laboratory biomarker analysis

Correlative studies

药品：sorafenib tosylate

Given PO

其他名称：
  • 海湾 43-9006
  • BAY 43-9006 甲苯磺酸盐
  • 海湾 54-9085
  • 多吉美
  • 单频网
安慰剂比较：Arm II (placebo)

Patients receive placebo PO BID.
其他：laboratory biomarker analysis

Correlative studies

其他：placebo

Given PO

其他名称：
  • PLCB

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Recurrence-free Survival at 2 Years
大体时间：Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 2 years

Recurrence-free Survival at 2 Years: The number of participants who were alive without recurrence of hepatocellular carcinoma (HCC). Recurrence-free survival was defined as the time from randomization to the first documented HCC recurrence or death from any cause, whichever occurred first.
Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 2 years

次要结果测量

结果测量
措施说明
大体时间
Recurrence-free Survival at One Year
大体时间：Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 1 year

Recurrence-free Survival at One Year: The number of participants who were alive without recurrence of hepatocellular carcinoma (HCC). Recurrence-free survival was defined as the time from randomization to the first documented HCC recurrence or death from any cause, whichever occurred first.
Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 1 year
Overall Survival
大体时间：From randomization through the last available follow-up, approximately two years

The number of participants who were alive at the last available follow-up. Overall survival was defined as the time from randomization to death from any cause or the last date the participant was known to be alive.
From randomization through the last available follow-up, approximately two years
Graft Failure Free Survival
大体时间：From randomization through the end of study follow-up, approximately two years

Graft Failure Free Survival: The number of participants who remained alive without failure of the transplanted liver. Graft-failure-free survival was defined as the time from randomization to the first documented graft failure according to local clinical standards.
From randomization through the end of study follow-up, approximately two years
Serum Alpha-fetoprotein (AFP) Correlation to Recurrence
大体时间：From randomization through the end of study follow-up, approximately two years

Serum Alpha-fetoprotein (AFP) Correlation to Recurrence: Among participants who experienced hepatocellular carcinoma (HCC) recurrence, this outcome assessed whether serum alpha-fetoprotein (AFP), a blood biomarker used to monitor HCC, was associated with recurrence.
From randomization through the end of study follow-up, approximately two years
Serum Alpha-fetoprotein (AFP) 24 Months
大体时间：Assessed at two years

Serum Alpha-fetoprotein (AFP) 24 Months: Serum alpha-fetoprotein (AFP), a blood biomarker used to monitor hepatocellular carcinoma (HCC), was measured during follow-up. Results are reported as the median AFP level at 24 months.
Assessed at two years
Adverse Events Assessed in Terms of Seriousness, Severity, and Relationship to the Study Material According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
大体时间：Assessed from randomization through up to 30 days after last drug dose, approximately two years

See section four, Adverse events and serious adverse events
Assessed from randomization through up to 30 days after last drug dose, approximately two years
Impact of Sorafenib-Tacrolimus Interactions
大体时间：During the 24-month study treatment periodmeasured at 24 months

Median tacrolimus levels (ng/mL) measured at 24 months
During the 24-month study treatment periodmeasured at 24 months
Wound Complications
大体时间：During the 24-month study treatment period

Impact of therapy on wound healing
During the 24-month study treatment period
Hepatitis C Viral Recurrence
大体时间：During the 24-month study treatment period

data was insufficient to analyze the impact of Hepatitis C viral recurrence
During the 24-month study treatment period

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Jonsson Comprehensive Cancer Center

合作者

Bayer

调查人员

  • 首席研究员：Fady Kaldas, MD、Jonsson Comprehensive Cancer Center

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2012年11月8日

初级完成 (实际的)

2023年2月1日

研究完成 (实际的)

2023年2月1日

研究注册日期

首次提交

2012年6月18日

首先提交符合 QC 标准的

2012年6月19日

首次发布 (估计的)

2012年6月20日

研究记录更新

最后更新发布 (实际的)

2026年11月3日

上次提交的符合 QC 标准的更新

2026年10月9日

最后验证

2023年2月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • 11-003311
  • NCI-2012-00911 (注册表标识符：CTRP (Clinical Trial Reporting Program))

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

订阅